同源框蛋白質NANOG

同源框蛋白質NANOG
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	2KT0
識別號
別名	NANOG；, entrez:79923, Nanog, Nanog homeobox
外部ID	OMIM：607937 MGI：1919200 HomoloGene：78027 GeneCards：NANOG
基因位置（人類）
染色體	12號染色體
終止	7,799,146 bp
基因位置（小鼠）
染色體	小鼠6號染色體
終止	122,691,592 bp
RNA表現模式
	查閱更多表現資料
基因本體
分子功能	• DNA結合轉錄因子活性; • DNA結合; • sequence-specific DNA binding; • 血漿蛋白結合; • transcription corepressor activity; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • DNA-binding transcription activator activity, RNA polymerase II-specific; • DNA-binding transcription factor activity, RNA polymerase II-specific; • RNA polymerase II cis-regulatory region sequence-specific DNA binding;
細胞組分	• 核仁; • 細胞核; • 核質;
生物學過程	• 基因調節; • regulation of cell differentiation; • multicellular organism development; • 細胞分化; • 細胞增殖; • regulation of transcription, DNA-templated; • somatic stem cell population maintenance; • transcription, DNA-templated; • positive regulation of transcription by RNA polymerase II; • endodermal cell fate specification; • negative regulation of nucleic acid-templated transcription; • stem cell population maintenance; • transcription by RNA polymerase II; • cytokine-mediated signaling pathway; • regulation of transcription by RNA polymerase II; • positive regulation of stem cell proliferation;
	Sources:Amigo / QuickGO
直系同源
	79923
	71950
	ENSG00000111704
	ENSMUSG00000012396
	Q9H9S0
	Q80Z64
	NM_001297698; NM_024865
	NM_028016; NM_001289828; NM_001289830; NM_001289831
	NP_001284627; NP_079141
	NP_001276757; NP_001276759; NP_001276760; NP_082292
	維基資料
檢視/編輯人類	檢視/編輯小鼠

NANOG（讀法：nanOg）是一種對未分化的胚胎幹細胞（ESC）自我更新至關重要的轉錄因子。人體的NANOG蛋白質由NANOG基因編碼^[5]^[6]。

Quick Facts 同源框蛋白質NANOG, 已知的結構 ...

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結構

人類NANOG蛋白質是一種長305胺基酸殘基的蛋白質，擁有一個長約60胺基酸殘基的DNA結合同源域（homeodomain, HD）以及一個無規則的N端。NANOG的同源結構域由三個α螺旋以及一些連結這些α螺旋的環結構組成。儘管Nanog蛋白在脊椎動物中保守性不強，但是其同源結構域卻擁有很強保守性^[7]^[8]。

功能

NANOG對胚胎幹細胞幹性的維持至關重要。NANOG能夠與Sox2、Oct4共同作用，通過形成一個表現特異基因的轉錄網絡，維持胚胎幹細胞的自我更新能力，並抑制胚胎幹細胞的分化^[9]^[10]。

研究進展

基礎生物學理論

鼠胚胎幹細胞中Nanog的過表達能夠使這類細胞能夠在無白血病抑制因子（Leukemia inhibitory factor, LIF）的環境中維持的自我更新能力^[11]，過表現NANOG的人胚胎幹細胞能夠在多次傳代後仍然保持幹性。敲低Nanog基因的表現能夠促進胚胎幹細胞的分化^[12]。

如果Nanog蛋白不表現或失去功能，鼠胚胎幹細胞會分化成其他類型的細胞^[5]^[6]^[13]。

已證明腫瘤抑制因子p53能夠與NANOG基因的啟動子結合，並能夠在鼠胚胎幹細胞DNA受損後抑制NANOG基因的表現。因此，p53能夠通過p53依賴細胞周期阻滯以及自噬誘導胚胎幹細胞的分化^[13]。

Nanog基因能夠使得NIH3T3細胞的生長加快，並表現出能夠在軟洋菜上形成細胞集落等等與原來不同的特性^[14]。

一部分腫瘤細胞或腫瘤幹細胞會表現NANOG蛋白^[15]^[16]。

進化生物學

人類和黑猩猩的基因組共享10個位置相同的NANOG蛋白假基因，其中一個是基因重複造成，另外九個為反轉錄產生的假基因（retropseudogenes）。在九個NANOG反轉錄假基因中，有兩個缺乏Poly-A尾，說明在它們的產生過程中可能發生了複製錯誤。且因為同一種假基因在兩個不相關的基因組中出現，還包含相同複製錯誤的機會極低，此一事實提供了一個人與黑猩猩之間演化的證據^[17]。

命名

成功分離鼠Nanog基因的伊恩·錢伯斯（Ian Chambers）教授這樣說：「Nanog似乎是一種擁有決定胚胎幹細胞能在實驗室中生長的能力的基因，也就是說它能夠使得幹細胞『長生不老』，因此，我用「Tír na nÓg」（提爾納諾，愛爾蘭神話中的異世界）來命名這種蛋白質/基因。」^[18]。

參考文獻

[1]
GRCh38: Ensembl release 89: ENSG00000111704 - Ensembl, May 2017
[2]
GRCm38: Ensembl release 89: ENSMUSG00000012396 - Ensembl, May 2017
[3]
Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
[4]
Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
[5]
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. May 2003, 113 (5): 631–42. PMID 12787504. doi:10.1016/S0092-8674(03)00393-3.
[6]
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.
[7]
Gehring WJ et al. Homeodomain-DNA recognition. Cell. 1994, 78 (2): 211–223.
[8]
Gehring WJ, Affolter M, Bürglin T. Homeodomain protein. Annu Rev Biochem. 1994, (63): 487–526.
[9]
NANOG Nanog homeobox [ Homo sapiens (human) ]. NCBI. [2016-12-18]. （原始內容存檔於2020-09-22）.
[10]
Boiani M, Schöler HR. Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005-12, 6 (11): 872–84.
[11]
Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. Mar 2006, 133 (6): 1193–201. PMID 16501172. doi:10.1242/dev.02286.
[12]
Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells. Mar 2005, 23 (3): 299–305. PMID 15749924. doi:10.1634/stemcells.2004-0252.
[13]
Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, Xu Y. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nature Cell Biology. Feb 2005, 7 (2): 165–71. PMID 15619621. doi:10.1038/ncb1211.
[14]
Piestun D, Kochupurakkal BS, Jacob-Hirsch J, Zeligson S, Koudritsky M, Domany E, Amariglio N, Rechavi G, Givol D. Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochemical and Biophysical Research Communications. Apr 2006, 343 (1): 279–85. PMID 16540082. doi:10.1016/j.bbrc.2006.02.152.
[15]
Gong, Shuai et al. Regulation of NANOG in cancer cells.. Molecular Carcinogenesis 54.9(2015):679–687.
[16]
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.
[17]
Daniel J. Fairbanks. Relics of Eden: The Powerful Evidence of Evolution in Human DNA. Buffalo, N.Y: Prometheus Books. 2007: 94–96, 177–182. ISBN 1-59102-564-8.
[18]
ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth. [2007-07-26]. （原始內容存檔於2012-03-25）.

延伸閱讀

Cavaleri F, Schöler HR. Nanog: a new recruit to the embryonic stem cell orchestra. Cell. May 2003, 113 (5): 551–2. PMID 12787492. doi:10.1016/S0092-8674(03)00394-5.
Constantinescu S. Stemness, fusion and renewal of hematopoietic and embryonic stem cells. Journal of Cellular and Molecular Medicine. 2004, 7 (2): 103–12. PMID 12927049. doi:10.1111/j.1582-4934.2003.tb00209.x.
Pan G, Thomson JA. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Research. Jan 2007, 17 (1): 42–9. PMID 17211451. doi:10.1038/sj.cr.7310125.
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. May 2003, 113 (5): 631–42. PMID 12787504. doi:10.1016/S0092-8674(03)00393-3.
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.
Clark AT, Rodriguez RT, Bodnar MS, Abeyta MJ, Cedars MI, Turek PJ, Firpo MT, Reijo Pera RA. Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells. 2004, 22 (2): 169–79. PMID 14990856. doi:10.1634/stemcells.22-2-169.
Hart AH, Hartley L, Ibrahim M, Robb L. Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. Developmental Dynamics. May 2004, 230 (1): 187–98. PMID 15108323. doi:10.1002/dvdy.20034.
Booth HA, Holland PW. Eleven daughters of NANOG. Genomics. Aug 2004, 84 (2): 229–38. PMID 15233988. doi:10.1016/j.ygeno.2004.02.014.
Hatano SY, Tada M, Kimura H, Yamaguchi S, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T. Pluripotential competence of cells associated with Nanog activity. Mechanisms of Development. Jan 2005, 122 (1): 67–79. PMID 15582778. doi:10.1016/j.mod.2004.08.008.
Deb-Rinker P, Ly D, Jezierski A, Sikorska M, Walker PR. Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation. The Journal of Biological Chemistry. Feb 2005, 280 (8): 6257–60. PMID 15615706. doi:10.1074/jbc.C400479200.
Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells. Mar 2005, 23 (3): 299–305. PMID 15749924. doi:10.1634/stemcells.2004-0252.
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.
Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M. Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells. Sep 2005, 23 (8): 1035–43. PMID 15983365. doi:10.1634/stemcells.2005-0080.
Oh JH, Do HJ, Yang HM, Moon SY, Cha KY, Chung HM, Kim JH. Identification of a putative transactivation domain in human Nanog. Experimental & Molecular Medicine. Jun 2005, 37 (3): 250–4. PMID 16000880. doi:10.1038/emm.2005.33.
Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. Sep 2005, 122 (6): 947–56. PMC 3006442 . PMID 16153702. doi:10.1016/j.cell.2005.08.020.
Kim JS, Kim J, Kim BS, Chung HY, Lee YY, Park CS, Lee YS, Lee YH, Chung IY. Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog. Experimental & Molecular Medicine. Dec 2005, 37 (6): 601–7. PMID 16391521. doi:10.1038/emm.2005.73.
Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. Mar 2006, 133 (6): 1193–201. PMID 16501172. doi:10.1242/dev.02286.

外部連結

醫學主題詞表（MeSH）：NANOG+protein,+human
醫學主題詞表（MeSH）：Nanog+protein,+mouse
FactorBook NANOG
Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells. Young Lab. Whitehead Institute for Biomedical Research. [2009-02-28]. （原始內容存檔於2009-06-28）.
Jaenisch Lab Research Summary. Whitehead Institute. [2009-02-28]. （原始內容存檔於2012-06-26）.
Discovery reveals more about stem cells' immortality

參見

[refGRCh38Ensembl-1] [1]
GRCh38: Ensembl release 89: ENSG00000111704 - Ensembl, May 2017

[refGRCm38Ensembl-2] [2]
GRCm38: Ensembl release 89: ENSMUSG00000012396 - Ensembl, May 2017

[3] [3]
Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] [4]
Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid12787504-5] [5]
Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. May 2003, 113 (5): 631–42. PMID 12787504. doi:10.1016/S0092-8674(03)00393-3.

[pmid12787505-6] [6]
Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. May 2003, 113 (5): 643–55. PMID 12787505. doi:10.1016/S0092-8674(03)00392-1.

[7] [7]
Gehring WJ et al. Homeodomain-DNA recognition. Cell. 1994, 78 (2): 211–223.

[8] [8]
Gehring WJ, Affolter M, Bürglin T. Homeodomain protein. Annu Rev Biochem. 1994, (63): 487–526.

[9] [9]
NANOG Nanog homeobox [ Homo sapiens (human) ]. NCBI. [2016-12-18]. （原始內容存檔於2020-09-22）.

[10] [10]
Boiani M, Schöler HR. Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005-12, 6 (11): 872–84.

[pmid16501172-11] [11]
Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. Mar 2006, 133 (6): 1193–201. PMID 16501172. doi:10.1242/dev.02286.

[pmid15749924-12] [12]
Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells. Mar 2005, 23 (3): 299–305. PMID 15749924. doi:10.1634/stemcells.2004-0252.

[pmid15619621-13] [13]
Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, Xu Y. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nature Cell Biology. Feb 2005, 7 (2): 165–71. PMID 15619621. doi:10.1038/ncb1211.

[pmid16540082-14] [14]
Piestun D, Kochupurakkal BS, Jacob-Hirsch J, Zeligson S, Koudritsky M, Domany E, Amariglio N, Rechavi G, Givol D. Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochemical and Biophysical Research Communications. Apr 2006, 343 (1): 279–85. PMID 16540082. doi:10.1016/j.bbrc.2006.02.152.

[15] [15]
Gong, Shuai et al. Regulation of NANOG in cancer cells.. Molecular Carcinogenesis 54.9(2015):679–687.

[pmid15982323-16] [16]
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. Jul 2005, 47 (1): 48–56. PMID 15982323. doi:10.1111/j.1365-2559.2005.02182.x.

[isbn1-59102-564-8-17] [17]
Daniel J. Fairbanks. Relics of Eden: The Powerful Evidence of Evolution in Human DNA. Buffalo, N.Y: Prometheus Books. 2007: 94–96, 177–182. ISBN 1-59102-564-8.

[18] [18]
ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth. [2007-07-26]. （原始內容存檔於2012-03-25）.

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